反应详情

温度

75 °C

To a solution of (R)-benzyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (65.2 mg, 0.082 mmol) in THF (1.5 mL) and MeOH (0.5 mL) was added 3N lithium hydroxide (0.136 mL, 0.409 mmol). The reaction mixture was stirred at 75° C. for 3 h and then cooled to rt. The reaction content was subjected to reverse phase HPLC purification using prep-HPLC method 6 and dried under vacuum to give (R)-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylic acid (48.2 mg, 0.049 mmol, 59.9% yield) as a white solid. LC/MS: m/e 707.5 (M+H)+, 4.07 min (method 8). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 5.33 (br. s., 1H), 5.21-5.13 (m, 1H), 4.77 (s, 1H), 4.70 (s, 1H), 3.98 (br. s., 1H), 3.64 (br. s., 1H), 3.40-3.34 (m, 1H), 3.30-3.24 (m, 1H), 3.16 (dd, J=11.4, 3.8 Hz, 2H), 3.11-3.05 (m, 2H), 3.05-2.94 (m, 2H), 2.83-2.70 (m, 1H), 2.58 (d, J=12.2 Hz, 1H), 2.48 (ddt, J=17.4, 6.1, 2.9 Hz, 1H), 2.44-2.36 (m, 1H), 2.32-2.22 (m, 2H), 2.21-2.12 (m, 2H), 2.11-2.04 (m, 2H), 2.03-1.91 (m, 5H), 1.87-1.72 (m, 3H), 1.71 (s, 3H), 1.68-1.53 (m, 5H), 1.52-1.37 (m, 7H), 1.34 (s, 1H), 1.32-1.23 (m, 1H), 1.09 (s, 3H), 1.05 (s, 3H), 0.95 (s, 3H), 0.93 (s, 3H), 0.87 (s, 3H).

1. temperaturecooled to rt
2. customphase HPLC purification
3. customdried under vacuum